Effects of SGLT2I Therapy on Tubular Reabsorption and Tubular Epithelial Stress Injury in Patients With CKD.

Rationale & Objective: Sodium-glucose cotransporter-2 inhibitors (SGLT2I) are a standard of care treatment for chronic kidney disease (CKD). However, the effects of SGLT2I on tubular function and stress are rare. Study Design: A monocentric, prospective, observational study. Setting & Participants: Patients with CKD who were referred to the outpatient clinic of the Department of Nephrology at Göttingen University Hospital and for whom SGLT2I therapy was indicated as part of standard treatment were prospectively included and treated with SGLT2I in accordance with current guidelines. Analytical Approach: Urine samples were collected, and the levels of urinary α1-microglobulin (uα-1-MG), urinary Dickkopf-3 (uDKK3), and urinary albumin creatinine ratio (UACR), each normalized to urinary creatinine, were measured at baseline and after 6 months of therapy. Results: Total of 57 patients were included. The mean age was 66.4 ± 12.4 years; 42.1% were female. At baseline, mean estimated glomerular filtration rate was 42.0 ± 15.3 mL/min/1.73m Limitations: The small sample size, lack of a control group, and the short follow-up duration may restrict the findings. Conclusions: This study demonstrates an increase in uα-1-MG during SGLT2I treatment in patients with CKD, particularly in UACR stage A1, in which reduction of hyperfiltration is less pronounced. Because uDKK3 as a parameter of tubular damage remained stable, the increase in uα-1-MG may reflect a functional reduction of protein reabsorption and thus reduced intratubular protein overload as a potential nephroprotective effect.